Onapristone (ONA) is an anti-progestin drug and progesterone receptor antagonist which was originally developed for contraceptive use. However, it has demonstrated substantial activity in advanced breast cancer. It is thought that ONA binds to the progesterone receptor (PR), preventing the PR from binding to DNA, and thereby inhibits or eliminates PR-induced transcription. See e.g., Klijn et al., Progesterone antagonists and progesterone receptor modulation in the treatment of breast cancer, Steroids, v. 65, pp. 825-830 (2000); Jonat et al., The clinical efficacy of progesterone antagonists in breast cancer, Endocrine Therapy of Breast Cancer, pp. 117-124.
Onapristone is known to be an amorphous compound. For example, (3-Acyloxypropyl)-derivatives of onapristone are crystalline in comparison to the parent compound. Neef, G.; Wiechert, R.; Beier, S.; Elger, W.; Henderson, D. U.S. Pat. No. 4,780,461, 1988. Onapristone has previously been isolated as an amorphous solid and as a yellow oil. Neef, G.; Wiechert, R.; Beier, S.; Elger, W.; Henderson, D. Steroids, 1984, 44, 349; Neef, G Sauer, G.; Wiechert, R.; Beier, S.; Elger, W.; Henderson, D.; Rohde, R. DE3321826, 1984.
U.S. Pat. No. 4,843,157 refers to a process for stereoselection of the desired isomer by photochemical conversion. In this process, photochemical conversion is performed using a “conventional mercury high-pressure lamp” as the radiation source. The preferred wavelengths are identified as ranging from about 250 to about 350 nm. However, the process described in U.S. Pat. No. 4,843,157 (incorporated by reference herein in its entirety) achieved yields in the range of 45 to 60%. Photoconversion of intermediates in the synthesis of progesterone receptor antagonists has also been performed with a mercury lamp at wavelengths of 250-580 nm. See, e.g., Guohua et al., Synthesis of Progesterone Receptor Antagonist ZK98299, Zhongguo Yaoke Daxue Xuebao (1992), 23(4), 209-12.
What is needed is an improved, less costly method for making, forming, or synthesizing onapristone and related compounds with fewer impurities, and fewer and simpler steps.